Jefferies 2017 Healthcare Conference June 9, 2017 Nasdaq : BLUE 1
Forward Looking Statements These slides and the accompanying oral presentation contain forward-looking statements and information. The use of words such as may, might, will, should, expect, plan, anticipate, believe, estimate, project, intend, future, potential, or continue, and other similar expressions are intended to identify forward-looking statements. For example, all statements we make regarding the initiation, timing, progress and results of our preclinical and clinical studies and our research and development programs, our ability to advance product candidates into, and successfully complete, clinical studies, and the timing or likelihood of regulatory filings and approvals are forward looking. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These statements are also subject to a number of material risks and uncertainties that are described in our most recent annual report on Form 10-K, as well as our subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. 2
OUR VISION: Make Hope a Reality BLUE MOJO OUR PATIENTS OUR PEOPLE TRUE BLUE 3
World-class Gene Therapy Platform and Integrated Global Capabilities T H E G E N E T H E R A P Y P R O D U C T C O M P A N Y Patient Impact 2 + 2 + Products Programs Nearing 4 + on the Market Commercialization Additional Programs in the Clinic 4
bluebird Pipeline Overview COLLABORATORS 5
How Do We Get There? Data, Execution and Development in 2017 LentiGlobin, TDT Update CRB-401 Study Data (bb2121) @ ASCO @ EHA LentiGlobin, TDT and SCD Update @ ASH File Next Generation BCMA IND (bb21217) DATA DEVELOPMENT LentiD CALD Update @TBD Initiate HGB-212 Study of LentiGlobin EXECUTION Confirm LentiD, CALD Clinical/ Regulatory Path Advance & Further Validate Gene Editing Platform Preparations for TDT EU MAA Filing 6
Despite Progress in Multiple Myeloma, There Remains a Need for New Therapies Preclinical and clinical studies leading to FDA approvals in MM 2006 Thalidomide 2012, 2015 Carfilzomib 2015 Panobinostat 2005 2010 2015 2003, 2005, 2008 Bortezomib (BTZ) 2007 Doxil + BTZ 2013, 2015 Pomalidomide 2015 Ixazomib 2006, 2014 Lenalidomide 2015 Daratumumab 2015 Elotuzumab Immunomodulatory agent Proteasome inhibitor Monoclonal antibody HDAC inhibitor CCR Focus Kenneth C. Anderson Clin Cancer Res 2016;22:5419-5427 Despite the availability of these classes of drugs for the treatment of MM, a recent analysis of patients with relapsed and refractory MM (RRMM) who were double refractory to a PI and an IMiD or had relapsed after >3 prior lines of therapy, including the novel agents pomalidomide (third-generation IMiD) and carfilzomib (second-generation PI), showed a median overall survival (OS) of 8 months. Usmani, Blood 2016 7
Current U.S. Standard of Care in 3 rd /4 th Line Multiple Myeloma Current U.S. Standards of Care Pomalyst and dex. (Pomalyst Product Monograph) Daratumamab (Lancet 2016, Lonial, S) N 452 106 Inclusion Criteria 2 prior therapies (including REVLIMID and bortezomib) Relapsed and refractory multiple myeloma Disease progression on or within 60 days of last therapy Previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs Prior Tx 5 (2-14) 5 (2-14) CR Rate (%) <1% ~3% ORR (%) 23.5% 29% The existing SOC outcomes for 3 rd /4 th line are limited in efficacy and durability leaving a need for new options for patients in need of better results Deep MRD negative responses are desirable in earlier lines of therapy and have demonstrated a benefit in long term outcomes PFS (mos) 3.6 months 3.7 months 8
CRB-401 Open-label Phase 1 Clinical Study of bb2121 3 + 3 Dose Escalation of CAR + T Cells Study Status Consented N=35 CRB-401 is a phase 1 dose-escalation and dose response study in relapsed / refractory MM Objectives: Determine preliminary safety and efficacy and recommended phase 2 dose 50 patients planned, standard 3 + 3 dose escalation followed by expansion cohort Key eligibility criteria Relapsed / refractory MM with 3 prior lines of therapy (including PI and IMiD), or double refractory Measurable disease 50% BCMA expression by IHC Adequate bone marrow (ANC 1,000, platelet count 50,000), adequate renal and hepatic function Cells Collected N=24 Clinical deterioration prior to infusion N=3 Dosed N=21 1 Month Response Evaluation N=18 * bb2121 Successfully manufactured for all patients collected 9
Baseline Demographics, Clinical Characteristics and Treatment History 21 patients have received bb2121 as of the data cut-off of May 4, 2017. Median follow-up is 15.4 weeks (range 1.4 to 54.4). Parameter Demographics and Clinical Characteristics Statistic N=21 Dosed Patients Age years Median (range) 58 (37-74) Male gender N (%) 13 (62%) Time since diagnosis (years) Median (range) 5 (1-16) ECOG 1 = 0 N (%) 10 (48%) ISS 2 Stage I II III High-risk cytogenetics (del17p, t(4;14), t(14;16), 1q, del 13) N (%) 6 (29%) 11 (52%) 4 (19%) N (%) 14 (67%) 1 ECOG: Eastern Cooperative Oncology Group Performance Score 2 ISS: International Staging System 3 SCT: Stem Cell Transplant Parameter MM Treatment History Statistic N=21 Dosed Patients Prior lines of therapy Median (range) 7 (3-14) Prior autologous SCT 3 N (%) 21 (100%) Prior Therapies Exposed Refractory Bortezomib 100% 67% Carfilzomib 91% 57% Lenalidomide 100% 86% Pomalidomide 91% 71% Daratumumab 71% 48% Cumulative Exposure Exposed Refractory Bort / Len 100% 67% Bort / Len / Car 91% 48% Bort / Len / Pom 91% 57% Bort / Len / Car / Pom 86% 43% Bort / Len / Car / Pom / Dara 71% 29% 10
bb2121 Generally Well Tolerated Treatment-Emergent Adverse Events in >2 Patients (N=21 Patients Dosed) No dose-limiting toxicities (DLTs) observed as of data cut-off Cytopenias related to Cy/Flu lymphodepletion 1 unrelated death due to cardio pulmonary arrest in a patient with an extensive cardiac history, the event occurred over 4 months after bb2121 infusion. The patient had achieved a stringent CR at 1 month and remained in remission at time of event 11 patients experienced 1 or more SAEs. SAEs occurring in more than 1 patient were CRS* Grade 1-2 that required hospitalization per protocol (N=4) and pyrexia (N=2) *CRS uniformly graded according to Lee et al., Blood 2014;124:188-195 11
Cytokine Release Syndrome Readily Manageable 15/21 (71%) with cytokine release syndrome (CRS) 2 patients with Grade 3 CRS that resolved in 24 hours 4 patients received tocilizumab, 1 (Grade 2 CRS) with steroids CRS grade does not appear related to tumor burden CRS-related symptoms mostly Grade 1-2 No Grade 3/4 neurotoxicity 12
All Patients in Active Dose Cohorts Achieved an Objective Response, Duration up to 54 Weeks All Patients in Active Dose Cohorts Achieved an Objective Response, Duration up to 54 Weeks * High tumor burden (>50% bone marrow involvement) Includes unscheduled assessments. 13
Summary bb2121 has induced durable and deepening responses in a heavily pretreated population with relapsed/refractory multiple myeloma, including: 100% ORR, 73% VGPR or better, 27% CR (at doses > 50 x 10 6 ) MRD negative results in all evaluable patients (N=4) No disease progression in patients treated with doses > 50 x 10 6, with 1 patient past 1 year and 8 patients past 6 months To date, the safety profile of bb2121 has been manageable through doses as high as 800 x 10 6 The 2 reported events of grade 3 CRS resolved within 24 hours No grade 3/4 neurotoxicity reported These results will inform identification of the dose(s) to bring forward into the expansion phase of the study in future development Data as of Nov 18, 2016 14
LentiGlobin TDT Clinical Studies NORTHSTAR (HGB-204) Phase 1/2 multicenter study; all genotypes All 18 patients treated, with 6 months follow-up 2 patients have completed 2-year analysis HGB-205 (TDT and SCD) Phase 1/2 single-center study; all genotypes 4 TDT patients treated, with 11 33 months follow-up NORTHSTAR-2 (HGB-207) Phase 3, global, multi-center study; non-β 0 /β 0 genotypes N=15 adults and adolescents, and N=8 pediatric patients Open and enrolling NORTHSTAR-3 (HGB-212) Phase 3, multi-center, global study; β 0 /β 0 genotypes N=15 adults, adolescents and pediatric patients Initiation planned for 2017 Data as of Sept 16, 2016 15
Research-scale Results Demonstrate Increase in Drug Product VCN Across Genotypes no enhancement transduction enhancement 2.9 Percent of cells transduced: 77% Other genotypes β 0/ β 0 genotypes HGB-207 first patient Data as of Nov 30, 2016 Exploratory in vitro analysis conducted at research scale 16
EU and U.S. Registration Strategies EU Pursue CONDITIONAL APPROVAL in patients with non-β 0 /β 0 genotypes on the basis of data from ongoing Northstar & HGB- 205 studies, as well as available data from Northstar-2 study ADAPTIVE PATHWAYS PRIME DESIGNATION U.S. Pursue approval in adults and adolescents based on data from ongoing pivotal HGB-207 trial Pediatric population to be included as a cohort of HGB- 207, rather than separate study Submission for approval in β 0/ β 0 patients to be based on planned HGB-212 study BREAKTHROUGH THERAPY DESIGNATION 17
Anti-Sickling Hemoglobin at Last Follow Up 48% Anti- Sickling Hb 7.9% 16.5% 30.0% 14.2% 18.3% 22.8% 18.7% Follow up (Months) 1301 1303 1304 1306 1308 1309 1310 1204 12 12 9 9 6 9 6 21 21 Data as of Sept 9, 2016 [HGB-205] and Nov 9, 2016 [HGB-206] 18
Vector copy number (VCN; per diploid genome) Vector Copy Number (VCN) in Drug Product and Peripheral Blood VCN drop from drug product to peripheral blood in HGB-206 Peripheral blood VCN over time 2. 5 3 2. 0 1204 2 1 0. 5 1. 5 1. 0 0. 5 0. 4 0. 3 0. 2 0. 1 1 3 0 1 1 3 0 3 1 3 0 4 1 3 0 6 1 3 0 8 1 3 0 9 1 3 1 0 1 2 0 4 0. 0 D P V C N P e r i p h e r a l V C N ( a t l a s t m e a s u r e m e n t ) 0. 0 0 3 6 9 1 2 1 5 1 8 2 1 2 4 M o n t h s P o s t D r u g P r o d u c t I n f u s i o n Data as of Sept 9, 2016 [HGB-205] and Nov 9, 2016 [HGB-206] 19
Protocol and Process Changes to Potentially Improve Outcomes in SCD Patients Hypoxic, inflamed marrow Pre-harvest transfusions to reduce marrow inflammation, hypoxia Low yield harvest Additional changes to manufacturing process to increase cell dose Poor transduction VCN Enhancers (Process 2) Inadequate myeloablation Increased exposure to myeloablative agent Apheresis (vs. bone marrow) Utilize Plerixafor for mobilization and collection 20
V C N ( v e c t o r c o p i e s / d i p l o i d g e n o m e ) LentiGlobin Manufacturing Process with Transduction Enhancers Increases DP VCN in SCD CD34+ Cells 4 no P renhancement o c e s s 1 transduction P r o c e s s 2enhancement 3.3 3 2 1 Percent of cells transduced: 83% 0 3 0 1 1 3 0 1 1 0 4 1 3 0 4 1 3 0 3 1 3 0 6 1 3 0 8 1 3 1 0 1 3 0 8 1 3 0 9 1 3 1 0 1 3 0 7 1 3 1 1 1 0 0 0 1 3 1 3 1 2 3 4 5 6 7 8 9 10 11 12 13 HGB-206 Research-scale SCD patient CD34+ cells transduced drug product Data as of Nov 30, 2016 21
Starbeam Study Ongoing Phase 2/3 Study Open label, multi-center, single arm, global study Design Primary Endpoint Secondary Endpoints 15 patients (18 enrolled) Age 17 Gad Positive Loes Score 0.5 9 NFS 1 No HLA-matched sibling donor % of Boys With Major Functional Disabilities at 24 Months After Transplant Neurological Functional Score (NFS) Gad +/- Loes Score Safety 22
2022 Vision The Gene Therapy Product Platform Patient Impact 2 + 2 + Products Programs Nearing 4 + on the Market Commercialization Additional Programs in the Clinic 23
Bringing & Valuing Hope Go TRUE BLUE 2022 We Must Make Hope a Reality 24